Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster

Astrid Jeibmann, Kristin Eikmeier, Anna Linge, Marcel Kool, Björn Koos, Jacqueline Schulz, Stefanie Albrecht, Kerstin Bartelheim, Michael C. Frühwald, Stefan M. Pfister, Werner Paulus and Martin Hasselblatt ()
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Astrid Jeibmann: Institute of Neuropathology, University Hospital Münster
Kristin Eikmeier: Institute of Neuropathology, University Hospital Münster
Anna Linge: Institute of Neuropathology, University Hospital Münster
Marcel Kool: German Cancer Research Center DKFZ
Björn Koos: Genetics and Pathology, Science for Life Laboratory, Uppsala University
Jacqueline Schulz: Institute of Neuropathology, University Hospital Münster
Stefanie Albrecht: Institute of Neuropathology, University Hospital Münster
Kerstin Bartelheim: Swabian Childrens’ Cancer Center, Childrens’ Hospital Augsburg and EU-RHAB Registry
Michael C. Frühwald: Swabian Childrens’ Cancer Center, Childrens’ Hospital Augsburg and EU-RHAB Registry
Stefan M. Pfister: German Cancer Research Center DKFZ
Werner Paulus: Institute of Neuropathology, University Hospital Münster
Martin Hasselblatt: Institute of Neuropathology, University Hospital Münster

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

Date: 2014
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DOI: 10.1038/ncomms5005

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